tbuckley/cabot-search huggingface dataset:
inMTSCCA: An Integrated Multi-Task Sparse Canonical Correlation Analysis for Multi-Omic Brain Imaging Genetics
Authors: Lei Du, Jin Zhang, Ying Zhao, Muheng Shang, Lei Guo, Junwei Han
Journal: Genomics Proteomics & Bioinformatics (2023)

Identifying genetic risk factors for Alzheimer's disease (AD) is an important research topic. To date, different endophenotypes, such as imaging-derived endophenotypes and proteomic expression-derived endophenotypes, have shown the great value in uncovering risk genes compared to case-control studies. Biologically, a co-varying pattern of different omics-derived endophenotypes could result from the shared genetic basis. However, existing methods mainly focus on the effect of endophenotypes alone; the effect of cross-endophenotype (CEP) associations remains largely unexploited. In this study, we used both endophenotypes and their CEP associations of multi-omic data to identify genetic risk factors, and proposed two integrated multi-task sparse canonical correlation analysis (inMTSCCA) methods, i.e., pairwise endophenotype correlation-guided MTSCCA (pcMTSCCA) and high-order endophenotype correlation-guided MTSCCA (hocMTSCCA). pcMTSCCA employed pairwise correlations between magnetic resonance imaging (MRI)-derived, plasma-derived, and cerebrospinal fluid (CSF)-derived endophenotypes as an additional penalty. hocMTSCCA used high-order correlations among these multi-omic data for regularization. To figure out genetic risk factors at individual and group levels, as well as altered endophenotypic markers, we introduced sparsity-inducing penalties for both models. We compared pcMTSCCA and hocMTSCCA with three related methods on both simulation and real (consisting of neuroimaging data, proteomic analytes, and genetic data) datasets. The results showed that our methods obtained better or comparable canonical correlation coefficients (CCCs) and better feature subsets than benchmarks. Most importantly, the identified genetic loci and heterogeneous endophenotypic markers showed high relevance. Therefore, jointly using multi-omic endophenotypes and their CEP associations is promising to reveal genetic risk factors. The source code and manual of inMTSCCA are available at https://ngdc.cncb.ac.cn/biocode/tools/BT007330.
The potential impact of novel tuberculosis vaccine introduction on economic growth in low- and middle-income countries: A modeling study
Authors: Allison Portnoy, Jean-Louis Arcand, Rebecca A. Clark, Chathika K. Weerasuriya, Christinah Mukandavire, Roel Bakker, Edith Patouillard, Nebiat Gebreselassie, Matteo Zignol, Mark Jit, Richard G. White, Nicolas A. Menzies
Journal: PLoS Medicine (2023)

Most individuals developing tuberculosis (TB) are working age adults living in low- and middle-income countries (LMICs). The resulting disability and death impact economic productivity and burden health systems. New TB vaccine products may reduce this burden. In this study, we estimated the impact of introducing novel TB vaccines on gross domestic product (GDP) growth in 105 LMICs.
Spatially resolved transcriptomic profiles reveal unique defining molecular features of infiltrative 5ALA-metabolizing cells associated with glioblastoma recurrence
Authors: Geoffroy Andrieux, Tonmoy Das, Michaela Griffin, Jakob Straehle, Simon M. L. Paine, Jürgen Beck, Melanie Boerries, Dieter H. Heiland, Stuart J. Smith, Ruman Rahman, Sajib Chakraborty
Journal: Genome Medicine (2023)

Spatiotemporal heterogeneity originating from genomic and transcriptional variation was found to contribute to subtype switching in isocitrate dehydrogenase-1 wild-type glioblastoma (GBM) prior to and upon recurrence. Fluorescence-guided neurosurgical resection utilizing 5-aminolevulinic acid (5ALA) enables intraoperative visualization of infiltrative tumors outside the magnetic resonance imaging contrast-enhanced regions. The cell population and functional status of tumor responsible for enhancing 5ALA-metabolism to fluorescence-active PpIX remain elusive. The close spatial proximity of 5ALA-metabolizing (5ALA +) cells to residual disease remaining post-surgery renders 5ALA + biology an early a priori proxy of GBM recurrence, which is poorly understood.
Prolonged fasting times reap greater geroprotective effects when combined with caloric restriction in adult female mice
Authors: Eleonora Duregon, Maria Emilia Fernandez, Jorge Martinez Romero, Clara Di Germanio, Meaghan Cabassa, Romaniya Voloshchuk, Margaux R. Ehrlich-Mora, Jacqueline M. Moats, Sarah Wong, Oye Bosompra, Annamaria Rudderow, Christopher H. Morrell, Simonetta Camandola, Nathan L. Price, Miguel A. Aon, Michel Bernier, Rafael de Cabo
Journal: Cell Metabolism (2023)
Transition to Self-compatibility Associated With Dominant <i>S</i>-allele in a Diploid Siberian Progenitor of Allotetraploid <i>Arabidopsis kamchatica</i> Revealed by <i>Arabidopsis lyrata</i> Genomes
Authors: Uliana K Kolesnikova, Alison Dawn Scott, Jozefien D Van de Velde, Robin Burns, Nikita P Tikhomirov, Ursula Pfordt, Andrew C Clarke, Levi Yant, Alexey P Seregin, Xavier Vekemans, Stefan Laurent, Polina Yu Novikova
Journal: Molecular Biology and Evolution (2023)

A transition to selfing can be beneficial when mating partners are scarce, for example, due to ploidy changes or at species range edges. Here, we explain how self-compatibility evolved in diploid Siberian Arabidopsis lyrata, and how it contributed to the establishment of allotetraploid Arabidopsis kamchatica. First, we provide chromosome-level genome assemblies for two self-fertilizing diploid A. lyrata accessions, one from North America and one from Siberia, including a fully assembled S-locus for the latter. We then propose a sequence of events leading to the loss of self-incompatibility in Siberian A. lyrata, date this independent transition to ∼90 Kya, and infer evolutionary relationships between Siberian and North American A. lyrata, showing an independent transition to selfing in Siberia. Finally, we provide evidence that this selfing Siberian A. lyrata lineage contributed to the formation of the allotetraploid A. kamchatica and propose that the selfing of the latter is mediated by the loss-of-function mutation in a dominant S-allele inherited from A. lyrata.
Mapping genetic variants for nonsense-mediated mRNA decay regulation across human tissues
Authors: Bo Sun, Liang Chen
Journal: Genome biology (2023)

Nonsense-mediated mRNA decay (NMD) was originally conceived as an mRNA surveillance mechanism to prevent the production of potentially deleterious truncated proteins. Research also shows NMD is an important post-transcriptional gene regulation mechanism selectively targeting many non-aberrant mRNAs. However, how natural genetic variants affect NMD and modulate gene expression remains elusive.
Reducing primary cesarean delivery rate through implementation of a smart intrapartum surveillance system
Authors: Po Jen Cheng, You Hung Cheng, Steven S. W. Shaw, Hung Chi Jang
Journal: npj Digital Medicine (2023)

Abstract The rapid changes in clinical maternity situations that occur in a labor and delivery unit can lead to unpredictable maternal and newborn morbidities. Cesarean section (CS) rate is a key indicator of the accessibility and quality of a labor and delivery unit. This retrospective cross-sectional study assesses the nulliparous, term, singleton, vertex (NTSV) cesarean delivery rates before and after the implementation of a smart intrapartum surveillance system. Research data were collected from the electronic medical records of a labor and delivery unit. The primary outcome was the CS rate of the NTSV population. The data of 3648 women admitted for delivery were analyzed. Of the studied deliveries, 1760 and 1888 occurred during the preimplementation and postimplementation periods, respectively. The CS rate for the NTSV population was 31.0% and 23.3% during the preimplementation and postimplementation periods, respectively, indicating a significant 24.7% ( p = 0.014) reduction in CS rate after the implementation of the smart intrapartum surveillance system (relative risk, 0.75; 95% confidence interval, 0.71–0.80). In the NTSV population, the vaginal and CS birth groups, no significant difference in terms of newborn weight, neonatal Apgar scores, composite neonatal adverse outcome indicator, and the occurrence of the following: neonatal intensive care unit admission, neonatal meconium aspiration, chorioamnionitis, shoulder dystocia, perineal laceration, placental abruption, postpartum hemorrhage, maternal blood transfusion, and hysterectomy before and after the implementation of the smart intrapartum surveillance system. This study reveals that the use of the smart intrapartum surveillance system can effectively reduce the primary CS rate for low-risk NTSV pregnancies without significantly affecting perinatal outcomes.
GreenHill: a de novo chromosome-level scaffolding and phasing tool using Hi-C
Authors: Shun Ouchi, Rei Kajitani, Takehiko Itoh
Journal: Genome biology (2023)

Abstract Chromosome-level haplotype-resolved genome assembly is an important resource in molecular biology. However, current de novo haplotype assemblers require parental data or reference genomes and often fail to provide chromosome-level results. We present GreenHill, a novel scaffolding and phasing tool that considers various assemblers’ contigs as input to reconstruct chromosome-level haplotypes using Hi-C without parental or reference data. Its unique functions include new error correction based on Hi-C contacts and the simultaneous use of Hi-C and long reads. Benchmarks reveal that GreenHill outperforms other approaches in contiguity and phasing accuracy, and the majority of chromosome arms are entirely phased.
British Thoracic Society Clinical Statement on pleural procedures
Authors: Rachelle Asciak, Eihab O Bedawi, Rahul Bhatnagar, Amelia O Clive, Maged Hassan, Heather Lloyd, Raja Reddy, Helen Roberts, Najib M Rahman
Journal: Thorax (2023)

of clInIcal practIce poIntS Safety and preparation for pleural procedures► Before carrying out a pleural procedure, safety and preparation should be taken into consideration. Research questions• Studies to investigate the role of fibrinolytic treatment in septated effusion related to IPC use in MPE patients.• Studies addressing the use of single or dual stiches after IPC insertion.
CMOT: Cross-Modality Optimal Transport for multimodal inference
Authors: Sayali Anil Alatkar, Daifeng Wang
Journal: Genome biology (2023)

Multimodal measurements of single-cell sequencing technologies facilitate a comprehensive understanding of specific cellular and molecular mechanisms. However, simultaneous profiling of multiple modalities of single cells is challenging, and data integration remains elusive due to missing modalities and cell-cell correspondences. To address this, we developed a computational approach, Cross-Modality Optimal Transport (CMOT), which aligns cells within available multi-modal data (source) onto a common latent space and infers missing modalities for cells from another modality (target) of mapped source cells. CMOT outperforms existing methods in various applications from developing brain, cancers to immunology, and provides biological interpretations improving cell-type or cancer classifications.
Prevalence and predictors of data and code sharing in the medical and health sciences: systematic review with meta-analysis of individual participant data
Authors: Daniel G Hamilton, Kyungwan Hong, Hannah Fraser, Anisa Rowhani-Farid, Fiona Fidler, Matthew J Page
Journal: BMJ (2023)

To synthesise research investigating data and code sharing in medicine and health to establish an accurate representation of the prevalence of sharing, how this frequency has changed over time, and what factors influence availability.
Endoglin, a Novel Biomarker and Therapeutical Target to Prevent Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis
Authors: Teresa González-Muñoz, Angela Di Giannatale, Susana García-Silva, Vanesa Santos, Sara Sánchez-Redondo, Claudia Savini, Osvaldo Graña-Castro, Carmen Blanco-Aparicio, Suzanne Fischer, Olivier De Wever, Edgar Creus-Bachiller, Sara Ortega-Bertran, David J. Pisapia, Jose L. Rodríguez-Peralto, Juana Fernández-Rodríguez, Cleofé Romagosa Pérez-Portabella, Rita Alaggio, Maria Serena Benassi, Laura Pazzaglia, Katia Scotlandi, Nancy Ratner, Kaleb Yohay, Charles P. Theuer, Héctor Peinado
Journal: Clinical Cancer Research (2023)

Malignant peripheral nerve sheath tumors (MPNST) are highly aggressive soft-tissue sarcomas that lack effective treatments, underscoring the urgent need to uncover novel mediators of MPNST pathogenesis that may serve as potential therapeutic targets. Tumor angiogenesis is considered a critical event in MPNST transformation and progression. Here, we have investigated whether endoglin (ENG), a TGFβ coreceptor with a crucial role in angiogenesis, could be a novel therapeutic target in MPNSTs.ENG expression was evaluated in human peripheral nerve sheath tumor tissues and plasma samples. Effects of tumor cell-specific ENG expression on gene expression, signaling pathway activation and in vivo MPNST growth and metastasis, were investigated. The efficacy of ENG targeting in monotherapy or in combination with MEK inhibition was analyzed in xenograft models.ENG expression was found to be upregulated in both human MPNST tumor tissues and plasma-circulating small extracellular vesicles. We demonstrated that ENG modulates Smad1/5 and MAPK/ERK pathway activation and pro-angiogenic and pro-metastatic gene expression in MPNST cells and plays an active role in tumor growth and metastasis in vivo. Targeting with ENG-neutralizing antibodies (TRC105/M1043) decreased MPNST growth and metastasis in xenograft models by reducing tumor cell proliferation and angiogenesis. Moreover, combination of anti-ENG therapy with MEK inhibition effectively reduced tumor cell growth and angiogenesis.Our data unveil a tumor-promoting function of ENG in MPNSTs and support the use of this protein as a novel biomarker and a promising therapeutic target for this disease.
Fetal manipulation of maternal metabolism is a critical function of the imprinted Igf2 gene
Authors: Jorge Lopez-Tello, Hannah E.J. Yong, Ionel Sandovici, Georgina K.C. Dowsett, Efthimia R. Christoforou, Esteban Salazar-Petres, Rebecca Boyland, Tina Napso, Giles S.H. Yeo, Brian Y.H. Lam, Miguel Constancia, Amanda N. Sferruzzi-Perri
Journal: Cell Metabolism (2023)

Maternal-offspring interactions in mammals involve both cooperation and conflict. The fetus has evolved ways to manipulate maternal physiology to enhance placental nutrient transfer, but the mechanisms involved remain unclear. The imprinted Igf2 gene is highly expressed in murine placental endocrine cells. Here, we show that Igf2 deletion in these cells impairs placental endocrine signaling to the mother, without affecting placental morphology. Igf2 controls placental hormone production, including prolactins, and is crucial to establish pregnancy-related insulin resistance and to partition nutrients to the fetus. Consequently, fetuses lacking placental endocrine Igf2 are growth restricted and hypoglycemic. Mechanistically, Igf2 controls protein synthesis and cellular energy homeostasis, actions dependent on the placental endocrine cell type. Igf2 loss also has additional long-lasting effects on offspring metabolism in adulthood. Our study provides compelling evidence for an intrinsic fetal manipulation system operating in placenta that modifies maternal metabolism and fetal resource allocation, with long-term consequences for offspring metabolic health.
Machine learning for prediction of immunotherapeutic outcome in non-small-cell lung cancer based on circulating cytokine signatures
Authors: Feifei Wei, Koichi Azuma, Yoshiro Nakahara, Haruhiro Saito, Norikazu Matsuo, Tomoyuki Tagami, Taku Kouro, Yuka Igarashi, Takaaki Tokito, Terufumi Kato, Tetsuro Kondo, Shuji Murakami, Ryo Usui, Hidetomo Himuro, Shun Horaguchi, Kayoko Tsuji, Kenta Murotani, Tatsuma Ban, Tomohiko Tamura, Yohei Miyagi, Tetsuro Sasada
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Immune checkpoint inhibitor (ICI) therapy has substantially improved the overall survival (OS) in patients with non-small-cell lung cancer (NSCLC); however, its response rate is still modest. In this study, we developed a machine learning-based platform, namely the Cytokine-based ICI Response Index (CIRI), to predict the ICI response of patients with NSCLC based on the peripheral blood cytokine profiles. Methods We enrolled 123 and 99 patients with NSCLC who received anti-PD-1/PD-L1 monotherapy or combined chemotherapy in the training and validation cohorts, respectively. The plasma concentrations of 93 cytokines were examined in the peripheral blood obtained from patients at baseline (pre) and 6 weeks after treatment (early during treatment: edt). Ensemble learning random survival forest classifiers were developed to select feature cytokines and predict the OS of patients undergoing ICI therapy. Results Fourteen and 19 cytokines at baseline and on treatment, respectively, were selected to generate CIRI models (namely preCIRI14 and edtCIRI19), both of which successfully identified patients with worse OS in two completely independent cohorts. At the population level, the prediction accuracies of preCIRI14 and edtCIRI19, as indicated by the concordance indices (C-indices), were 0.700 and 0.751 in the validation cohort, respectively. At the individual level, patients with higher CIRI scores demonstrated worse OS [hazard ratio (HR): 0.274 and 0.163, and p&lt;0.0001 and p=0.0044 in preCIRI14 and edtCIRI19, respectively]. By including other circulating and clinical features, improved prediction efficacy was observed in advanced models (preCIRI21 and edtCIRI27). The C-indices in the validation cohort were 0.764 and 0.757, respectively, whereas the HRs of preCIRI21 and edtCIRI27 were 0.141 (p&lt;0.0001) and 0.158 (p=0.038), respectively. Conclusions The CIRI model is highly accurate and reproducible in determining the patients with NSCLC who would benefit from anti-PD-1/PD-L1 therapy with prolonged OS and may aid in clinical decision-making before and/or at the early stage of treatment.
Cold snare and ablation technique for endoscopic mucosal resection of incompletely resected large laterally spreading tumors
Authors: Roupen Djinbachian, Mahsa Taghiakbari, Mohammed El Mehdi El Yamani, Daniel von Renteln
Journal: Endoscopy (2023)

Previously attempted and partially resected laterally spreading tumors (PA-LSTs) present a particular challenge for subsequent endoscopic mucosal resection (EMR) owing to the presence of submucosal fibrosis. Techniques such as hot avulsion, or cold avulsion with adjuvant snare tip soft coagulation have been described previously, with local recurrence rates of 15 % [1] [2]. Hot EMR is challenging for PA-LSTs given that lesions are often nonlifting, which, combined with the nonrigid soft snare, makes capturing the mucosa difficult, hampering resection of these lesions [3]. The combination of cold EMR with ablation might prove to be a good combination. The rigidity of the cold snare offers the capacity to push firmly against mucosa, allowing for improved engagement of the snare in the submucosal plane and this can be combined with enhanced submucosal injection and ablation using hybrid argon plasma coagulation (hAPC) in the COld Snare with Ablation (COSA) technique [4].
Efficacy and cost-effectiveness of a novel dual grasping forceps-assisted over-the-scope clip inverted closure after gastric endoscopic full-thickness resection
Authors: Noriko Nishiyama, Shintaro Fujihara, Naoya Tada, Kaho Nakatani, Asahiro Morishita, Takayoshi Kishino, Hideki Kobara
Journal: Endoscopy (2023)

Achieving reliable full-thickness defect closure after gastric endoscopic full-thickness resection (EFTR) for gastrointestinal stromal tumors is challenging [1] [2]. Although mucosal closure appears clinically acceptable [2] [3] [4], it is crucial to develop a robust and technically easy closure method that enables serosa-serosa inverted closure, as with surgical sutures. Here, we describe a novel dual slim grasping forceps-assisted over-the-scope (OTS) clip closure under dual-channel endoscopy in gastric EFTR. With this technique, the difficult maneuvers and high cost associated with Twin Grasper forceps (Ovesco Endoscopy GmbH, Tübingen, Germany) can be overcome.
Large-balloon anchor technique for endoscopic retrograde cholangiopancreatography in a patient with esophageal hiatal hernia
Authors: Takao Iemoto, Yasutaka Yamada, Tomoo Yoshie, Hiroki Hayashi, Tetsuyuki Abe, Takayuki Ose
Journal: Endoscopy (2023)

Endoscopic retrograde cholangiopancreatography (ERCP) is primarily performed to remove common bile duct (CBD) stones. However, in patients with severe esophageal hiatal hernias, advancing the duodenoscope into the second portion of the duodenum may be challenging. We present a case in which a large-balloon anchor technique [1] was used during ERCP in a patient with a severe hiatal hernia.
Efficacy and safety of the novel capsid inhibitor lenacapavir to treat multidrug-resistant HIV: week 52 results of a phase 2/3 trial
Authors: Onyema Ogbuagu, Sorana Segal-Maurer, Winai Ratanasuwan, Anchalee Avihingsanon, Cynthia Brinson, Kimberly Workowski, Andrea Antinori, Yazdan Yazdanpanah, Benoit Trottier, Hui Wang, Nicolas Margot, Hadas Dvory-Sobol, Martin S Rhee, Jared M Baeten, Jean-Michel Molina, Edwin DeJesus, Gary J. Richmond, Mezgebe Berhe, Peter J. Ruane, Gary Ian Sinclair, Kenneth Lichtenstein, Moti N. Ramgopal, Andrew Wiznia, Kimberly Workowski, William Sanchez, Cynthia Brinson, Joseph P. McGowan, Catherine M. Creticos, Daniel S. Berger, David A. Wheeler, Debbie Hagins, Gordon E. Crofoot, James Sims, Olayemi Osiyemi, Theo Hodge, Christine Zurawski, Onyema Ogbuagu, Sorana Segal-Maurer, Winai Ratanasuwan, Anchalee Avihingsanon, Krittaecho Siripassorn, Ploenchan Chetchotisakd, Antonella Castagna, Andrea Antinori, Francesco Castelli, Sylvie Ronot-Bregigeon, Jean-Michel Molina, Yazdan Yazdanpanah, Benoit Trottier, Jason Brunetta, Takuma Shirasaka, Yoshiyuki Yokomaku, Ellen Koenig, Josep Mallolas, Hans-Jurgen Stellbrink, Chien-Ching Hung, Mohammed Rassool
Journal: The Lancet HIV (2023)
Sickle cell disease landscape and challenges in the EU: the ERN-EuroBloodNet perspective
Authors: María del Mar Mañú Pereira, Raffaella Colombatti, Federico Alvarez, Pablo Bartolucci, Celeste Bento, Angelo Loris Brunetta, Elena Cela, Soteroula Christou, Anna Collado, Mariane de Montalembert, Laurence Dedeken, Pierre Fenaux, Frédéric Galacteros, Andreas Glenthøj, Victoria Gutiérrez Valle, Antonis Kattamis, Joachim Kunz, Stephan Lobitz, Corrina McMahon, Mariangela Pellegrini, Sara Reidel, Giovanna Russo, Miriam Santos Freire, Eduard van Beers, Petros Kountouris, Béatrice Gulbis
Journal: The Lancet Haematology (2023)
Colorectal gel immersion endoscopic submucosal dissection using the tunneling method
Authors: Yuya Nakano, Takeshi Hatanaka, Yoichi Hazama, Yoshiki Tanaka, Yoko Hachisu, Tomoaki Tashima, Toshio Uraoka
Journal: Endoscopy (2023)

Colorectal endoscopic submucosal dissection (ESD) is now widely used for the treatment of colorectal tumors using several strategies. The effectiveness of the pocket-creation method combined with saline immersion has been reported with an improved endoscopic visual field and submucosal approach due to the buoyancy of the lesion and reduced the amount of submucosal injection. Its disadvantages include a poor visual field during bleeding and dissipation of coagulation ability with monopolar devices [1] [2]. However, gel immersion ESD has been reported to overcome these issues [3] [4] [5]. As the colorectum has a large lumen and may cause difficulties for gel immersion, it is assumed that a closed lumen such as a pocket or tunnel would facilitate gel immersion; therefore, the strategy of performing gel immersion ESD in combination with the tunneling method was devised.